PUBLIC HEALTH RELEVANCE: Alzheimer's disease is an age-related cognitive dysfunction that affects millions of people worldwide for which no cure currently exists. At the molecular level the aggregation of so-called amyloid peptides is proposed as one the major steps in the development and progression of the pathology. Insoluble forms of amyloid peptides, known as plaques, have been associated with Alzheimer's disease. However, soluble aggregates of amyloid peptides are believed to be the main neurotoxic species, which are responsible for the neuronal damage. Recognition of these soluble is an important, yet currently underdeveloped, area of research. We have recently discovered that certain fluorescent dyes can specifically recognize soluble neurotoxic forms of amyloid peptides. Based on these results, we propose to design and synthesize a structurally- and functionally-diverse library of the dyes using facile and efficient synthetic procedures. The lead compounds will be screened using various spectroscopic techniques in order to identify most specific and potent compounds for the recognition of soluble amyloid peptides. These studies are aimed at advancing our understanding of the nature of soluble amyloid species, which, subsequently, will aid in the development of anti-Alzheimer's medicine. The combination of synthetic, spectroscopic, biophysical approaches is likely to produce viable and significant results. Two graduate students will be involved in all aspects of the proposed research. The results obtained in the course of this research will be presented to the community at meetings and in publications, and they will constitute major parts of the graduate students'dissertations.